DIVERSE ACTIONS OF CALCITONIN-GENE-RELATED PEPTIDE ON INTRACELLULAR FREE CA2-106 OSTEOBLASTIC CELLS( CONCENTRATIONS IN UMR)

Calcitonin gene-related peptide (CGRP) was examined for its effects on intracellular free Ca2+ concentration ([Ca2+](i)) in UMR 106 osteobla st-like cells, Cells loaded with the Ca2+ dye FURA-2 dose-dependently responded to CGRP (1-100 nM) with transient two-fold increases in [Ca2 +](i), An intracellular source for this Ca2+ transient was suggested b y the failure of membrane depolarization with high extracellular K+ or acute depletion of extracellular Ca2+ ([Ca2+](e) with EGTA to attenua te this response, After cells were incubated for 45 min with 0.1 mM ex tracellular Ca2+ to deplete intracellular Ca2+ stores, CGRP produced a 25-30% decrease in [Ca2+](i) rather than a transient increase, This c alcium decrease was mimicked by membrane depolarization or by pinacidi l, a specific activator of adenosine triphosphate (ATP)-sensitive pota ssium (K-ATP channels, and blocked by glybenclamide, a specific blocke r of K-ATP channels. Our data suggest that CGRP has diverse Ca2+ regul atory effects in UMR 106 cells, mobilizing Ca2+ from intracellular sto res via classical signaling while possibly promoting cellular Ca2+ eff lux or inhibiting uptake through voltage-dependent Ca2+ channels via K -ATP-mediated hyperpolarization.